Sex Differences in the Control of Social Investigation and Anxiety by Vasopressin Cells of the Paraventricular Nucleus of the Hypothalamus

Neuroendocrinology. 2021;111(6):521-535. doi: 10.1159/000509421. Epub 2020 Jun 15.


The neuropeptide arginine-vasopressin (AVP) has long been implicated in the regulation of social behavior and communication in diverse taxa, but the source of AVP release relevant for behavior has not been precisely determined. Potential sources include hypothalamic cell populations such as the paraventricular (PVN), supraoptic, and suprachiasmatic nuclei, as well as extrahypothalamic cell groups in the extended amygdala. To address if AVP-expressing cells in the PVN are important for mouse social communication, we deleted PVN AVP-expressing cells using viral-mediated delivery of Cre-dependent caspase-9 cell death construct into the PVN of AVP-Cre-positive mice (expressing Cre-recombinase under the control of the AVP promoter) or AVP-Cre-negative littermate controls, and assessed their levels of social investigation, social communication, anxiety, sex behavior, and aggressive behavior. We found that these lesions increased social investigation in females, but not in males. However, in males but not in females, these lesions increased non-social anxiety-related behaviors in the elevated-plus maze. These results therefore point at differential involvement of PVN AVP-expressing cells in the context of social and emotional behavior in the two sexes, which may contribute to sex differences in social communication and anxiety disorders.

Keywords: Anxiety; Hypothalamus; Mice; Paraventricular nucleus of the hypothalamus; Sex differences; Social behavior; Social communication; Vasopressin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aggression / physiology*
  • Animals
  • Anxiety / physiopathology*
  • Arginine Vasopressin / metabolism*
  • Behavior, Animal / physiology*
  • Female
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Paraventricular Hypothalamic Nucleus / physiology*
  • Sex Characteristics*
  • Sexual Behavior, Animal / physiology
  • Social Behavior*


  • Arginine Vasopressin